Association of Human Leucocyte Antigen Class II, with viral load and immune response to Epstein–Barr virus in adult and pediatric Systemic lupus erythematosus patients

Das, Prabir; Minz, Ranjana Walker; Saikia, Biman; Sharma, Aman; Anand, Shashi; Singh, Heera; Singh, Surjit

doi:10.1177/09612033221100156

Cited by 3 publications

(3 citation statements)

References 47 publications

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“…EBV infects mature human B lymphocytes by binding to CD21 on the surface of B lymphocytes and entering the infected cells through receptor-mediated endocytosis. EBV infection may induce autoimmunity [ 23 , 25 ]. In recent years, attention has been given to the relationship between EBV infection and SLE.…”

Section: Discussionmentioning

confidence: 99%

Epstein‒Barr virus and human herpesvirus 6 infection in patients with systemic lupus erythematosus

Chen

et al. 2023

Virol J

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Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the etiology is still unclear. Some studies have indicated that viral infection might contribute to the development of SLE. Methods A total of 105 individuals with SLE and 110 matched healthy controls were tested for EBV-specific DNA fragments in peripheral blood monocytes by PCR-Southern blotting. The expression of EBV-encoded genes was determined by RT-PCR and Southern blotting in EBV-positive patients. Serum EBV-specific IgM antibody was determined by ELISA. HHV-6 DNA in peripheral blood monocytes of those SLE patients and normal controls was tested by nested PCR. Results Statistical analysis showed that the EBV-positive rate of SLE patients was significantly higher than that of the control group (χ2 = 87.329, P = 0), while the difference in the HHV-6-positive rate between the two groups was not significant (P > 0.05). An association of EBV and HHV-6 positivity in SLE patients was found (P = 0, r = 0.38). The EBV IgM level was significantly higher in SLE patients than in healthy controls (χ2 = 25.184, P = 0). Forty-two of the 75 EBV DNA-positive specimens were positive for EBNA2 mRNA, and an association between EBV EBNA2 mRNA and anti-Sm antibody positivity was found (P = 0, r = 0.409). LMP1 mRNA was positive in 2 SLE patients with active phase, and no LMP2A mRNA expression was detected in EBV DNA-positive specimens. EBV early gene BARF1 mRNA was detected in 2 cases of EBV-positive SLE patients, and these 2 patients were also HHV-6 DNA positive. Thirty-eight patients were BcLF1 mRNA positive, and 33 of them were HHV-6 positive as well. These factors were associated (χ2 = 15.734, P = 0). The expression of the EBV immediate early gene BZLF1 was negative in all 75 EBV-positive SLE patients. Conclusions The results suggest that EBV infection might be related to the occurrence of SLE. Although there is no direct evidence that HHV-6 infection is associated with the development of SLE, EBV and HHV-6 infection may have a coacceleration effect in SLE patients. This study provides a new theoretical and experimental basis for the study of viral etiology and the prevention and treatment of SLE.

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Section: Discussionmentioning

confidence: 99%

Epstein‒Barr virus and human herpesvirus 6 infection in patients with systemic lupus erythematosus

Chen

et al. 2023

Virol J

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“…The reasons for these discrepancies are not entirely clear and could be partly explained by the different methods used to determine EBV infection status. Most studies used a limited panel of EBV serological markers, mainly anti-VCA IgM, and/or anti-EA (D) IgG, and/or IgM, and few investigated a comprehensive EBV serological profile in lupus patients [ 21 , 22 , 23 ]. There is an even greater discrepancy in the data from studies reporting analyses of EBV DNA.…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr Virus Reactivation as a New Predictor of Achieving Remission or Lupus Low Disease Activity State in Patients with Systemic Lupus Erythematosus with Cutaneous Involvement

Mišković

Ćirković

Miljanovic

et al. 2023

IJMS

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Although Epstein–Barr virus (EBV) reactivation has long been associated with the pathogenesis of systemic lupus erythematosus (SLE), many aspects of this relationship remain unclear. Our objective was to investigate the association between EBV reactivation and the achievement of SLE remission and lupus low disease activity state (LLDAS) over a six-month period. Clinical, laboratory, and virological tests (anti-EBV antibodies and EBV DNA) were performed among 51 patients with the active form of SLE on two occasions six months apart. SLE remission and LLDAS achievement were assessed at the end of the follow-up period. Active EBV infection was detected in 45% of active SLE patients at baseline, and 77% transitioned to latent EBV infection at six months (p < 0.001). Multivariate regression revealed a higher titer of anti-EA(D) IgM-Abs and the presence of anti-EA(D) IgM-Abs as independent predictors of remission and LLDAS in SLE patients with mucocutaneous manifestations (p = 0.042) and rash only (p = 0.023), respectively. Since a higher C3 level was an independent predictor of transition to latent EBV infection (p = 0.027), the estimated cut-off value that could identify active SLE patients who will transition to latent EBV infection after six months was ≥0.780 g/L with a sensitivity of 70.6% and a specificity of 75.0% (AUC = 0.756, p = 0.003). EBV reactivation is common in patients with active SLE, and most of them transition to latent EBV infection after six months. Achieving remission and LLDAS in SLE patients with mucocutaneous manifestations can be predicted by a higher titer, whereas in SLE patients who have only a rash, the presence of anti-EA (D) IgM-Abs was a predictor of remission and LLDAS.

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“…Studies have suggested that active EBV replication may play a pathogenic role in NMOSD [20], as elevated levels of IgG antibodies to the early antigen were detected in a cohort of Japanese patients with NMO compared to MS and healthy controls (HCs) [20]. Interestingly, EBV has also been linked to several autoimmune disease associated with NMOSD [21], such as myasthenia gravis [22], systemic lupus erythematosus [23], and Sjogren's syndrome [24]. Various hypotheses surround this connection: EBV may induce molecular mimicry, where viral antigens resemble self-antigens, contributing to the development or exacerbation of the disease.…”

Section: Introductionmentioning

confidence: 99%

Epstein–Barr Virus and Human Endogenous Retrovirus in Japanese Patients with Autoimmune Demyelinating Disorders

Cossu,

Tomizawa,

Sechi

et al. 2023

IJMS

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Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocytes glycoprotein-antibody disease (MOGAD) are distinct autoimmune demyelinating disorders characterized by varying clinical and pathological characteristics. While the precise origins of these diseases remain elusive, a combination of genetic and environmental factors, including viral elements, have been suggested as potential contributors to their development. Our goal was to assess the occurrence of antibodies against pathogenic peptides associated with Epstein–Barr virus (EBV) and the human endogenous retrovirus-W (HERV-W) in serum samples obtained from Japanese individuals diagnosed with MS, NMOSD, and MOGAD and to make comparisons with a group of healthy controls (HCs). We conducted a retrospective analysis involving 114 Japanese participants, comprising individuals with MS (34), NMOSD (20), MOGAD (20), and HCs (40). These individuals were tested using a peptide-based enzyme-linked immunosorbent assay. A marked increase in antibody response against EBV nuclear antigen 1 (EBNA1)386–405 was observed in the serum of MS and MOGAD patients, as compared to HCs. Notably, we observed a correlation between antibodies against EBNA1386–405 and HERV-W486–504 peptides in a subset of the antibody-positive MS patients. These findings emphasize the involvement of EBV in the pathogenesis of MS and potentially MOGAD, suggesting its role in the reactivation of HERV-W.

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Association of Human Leucocyte Antigen Class II, with viral load and immune response to Epstein–Barr virus in adult and pediatric Systemic lupus erythematosus patients

Cited by 3 publications

References 47 publications

Epstein‒Barr virus and human herpesvirus 6 infection in patients with systemic lupus erythematosus

Epstein‒Barr virus and human herpesvirus 6 infection in patients with systemic lupus erythematosus

Epstein–Barr Virus Reactivation as a New Predictor of Achieving Remission or Lupus Low Disease Activity State in Patients with Systemic Lupus Erythematosus with Cutaneous Involvement

Epstein–Barr Virus and Human Endogenous Retrovirus in Japanese Patients with Autoimmune Demyelinating Disorders

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